Intestinal Epithelium Modulates Macrophage Response to Gliadin in Celiac Disease
Celiac disease is an immune-mediated enteropathy triggered by ingestion of gluten. Although its pathogenesis has been extensively studied and the contribution from both innate and adaptive immune responses has been reported, little is still known about the contribution of macrophages to the onset or...
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Frontiers Media S.A.
2019-11-01
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Series: | Frontiers in Nutrition |
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Online Access: | https://www.frontiersin.org/article/10.3389/fnut.2019.00167/full |
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doaj-6c87e9951bfa4909b6e0e1496ea6d8a4 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gloria Serena Gloria Serena Daniel Huynh Rosiane S. Lima Luciana M. Vise Rachel Freire Rachel Freire Laura Ingano Maureen M. Leonard Maureen M. Leonard Stefania Senger Stefania Senger Alessio Fasano Alessio Fasano Alessio Fasano |
spellingShingle |
Gloria Serena Gloria Serena Daniel Huynh Rosiane S. Lima Luciana M. Vise Rachel Freire Rachel Freire Laura Ingano Maureen M. Leonard Maureen M. Leonard Stefania Senger Stefania Senger Alessio Fasano Alessio Fasano Alessio Fasano Intestinal Epithelium Modulates Macrophage Response to Gliadin in Celiac Disease Frontiers in Nutrition celiac disease macrophages epithelium gliadin innate immunity |
author_facet |
Gloria Serena Gloria Serena Daniel Huynh Rosiane S. Lima Luciana M. Vise Rachel Freire Rachel Freire Laura Ingano Maureen M. Leonard Maureen M. Leonard Stefania Senger Stefania Senger Alessio Fasano Alessio Fasano Alessio Fasano |
author_sort |
Gloria Serena |
title |
Intestinal Epithelium Modulates Macrophage Response to Gliadin in Celiac Disease |
title_short |
Intestinal Epithelium Modulates Macrophage Response to Gliadin in Celiac Disease |
title_full |
Intestinal Epithelium Modulates Macrophage Response to Gliadin in Celiac Disease |
title_fullStr |
Intestinal Epithelium Modulates Macrophage Response to Gliadin in Celiac Disease |
title_full_unstemmed |
Intestinal Epithelium Modulates Macrophage Response to Gliadin in Celiac Disease |
title_sort |
intestinal epithelium modulates macrophage response to gliadin in celiac disease |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Nutrition |
issn |
2296-861X |
publishDate |
2019-11-01 |
description |
Celiac disease is an immune-mediated enteropathy triggered by ingestion of gluten. Although its pathogenesis has been extensively studied and the contribution from both innate and adaptive immune responses has been reported, little is still known about the contribution of macrophages to the onset or maintenance of the disease. Macrophages are extremely plastic immune cells that can be directed toward a pro- or anti-inflammatory phenotype by the surrounding microenvironment. Of note, gliadin, the most prominent causative agent of the disease, has been reported to trigger the production of pro-inflammatory cytokines in this cell population. In the present study, we aimed at investigating how the intestinal milieu and more specifically the epithelium can shape the macrophage response to gliadin. Using patient-derived organoids we showed that the intestinal epithelium derived from celiac disease donors releases anti-inflammatory factors that curb the macrophage response to gliadin. Furthermore, we uncovered that the celiac macrophages were better responders than macrophages derived from non-celiac controls. Finally, we demonstrated that IFNγ released by the epithelium is in part responsible of the observed anti-inflammatory effect. Our data shed light on the cross–talk between the immune system and the epithelium and its critical role in the intestinal homeostasis. Furthermore, we provide more evidence how alterations in the innate immune machinery in celiac patients may contribute to the onset of the disease. |
topic |
celiac disease macrophages epithelium gliadin innate immunity |
url |
https://www.frontiersin.org/article/10.3389/fnut.2019.00167/full |
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doaj-6c87e9951bfa4909b6e0e1496ea6d8a42020-11-25T01:36:17ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2019-11-01610.3389/fnut.2019.00167482289Intestinal Epithelium Modulates Macrophage Response to Gliadin in Celiac DiseaseGloria Serena0Gloria Serena1Daniel Huynh2Rosiane S. Lima3Luciana M. Vise4Rachel Freire5Rachel Freire6Laura Ingano7Maureen M. Leonard8Maureen M. Leonard9Stefania Senger10Stefania Senger11Alessio Fasano12Alessio Fasano13Alessio Fasano14Division of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesDivision of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, United StatesDivision of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, United StatesDivision of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, United StatesDivision of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesDivision of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, United StatesDivision of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesDivision of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesDivision of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesEuropean Biomedical Research Institute of Salerno, Salerno, ItalyCeliac disease is an immune-mediated enteropathy triggered by ingestion of gluten. Although its pathogenesis has been extensively studied and the contribution from both innate and adaptive immune responses has been reported, little is still known about the contribution of macrophages to the onset or maintenance of the disease. Macrophages are extremely plastic immune cells that can be directed toward a pro- or anti-inflammatory phenotype by the surrounding microenvironment. Of note, gliadin, the most prominent causative agent of the disease, has been reported to trigger the production of pro-inflammatory cytokines in this cell population. In the present study, we aimed at investigating how the intestinal milieu and more specifically the epithelium can shape the macrophage response to gliadin. Using patient-derived organoids we showed that the intestinal epithelium derived from celiac disease donors releases anti-inflammatory factors that curb the macrophage response to gliadin. Furthermore, we uncovered that the celiac macrophages were better responders than macrophages derived from non-celiac controls. Finally, we demonstrated that IFNγ released by the epithelium is in part responsible of the observed anti-inflammatory effect. Our data shed light on the cross–talk between the immune system and the epithelium and its critical role in the intestinal homeostasis. Furthermore, we provide more evidence how alterations in the innate immune machinery in celiac patients may contribute to the onset of the disease.https://www.frontiersin.org/article/10.3389/fnut.2019.00167/fullceliac diseasemacrophagesepitheliumgliadininnate immunity |